arco vic. 2004 (xiv) 96-102
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General Papers ARKIVOC 2004 (xiv) 96-102
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Synthesis and spectroscopic characterization of some
chromanochalcones and their dihydro derivatives
M. Srinivasa Rao,*a,b
J. Kotesh,a
R. Narukulla,c
and H. Duddeckd
aDepartment of Chemistry, Kakatiya University, Warangal, A. P., India
bDepartment of Biomedical Sciences, University of Rhode Island, Kingston, RI 02881, USA
cDepartment of Chemistry, The Open University, Walton Hall, Milton Keynes MK7 6AA,
England, UKdHannover University, Institute of Organic Chemistry, Schneiderberg 1B,
D-30167 Hannover, Germany
E-mail:srmeneni@mail.uri.edu
This paper is dedicated to Professor P. Srinivasa Rao on the occasion of 65th birthday
Abstract
Synthesis of naturally occurring 6-(,-dihydrocinnamoyl)-3,4-dihydro-2H-chromanes has been
carried out by the reaction of 6-acetyl-3,4-dihydro-2H-chromanes with methoxybenzaldehydes
followed by hydrogenation of the resulting 6-cinnamoyl-3,4-dihydro-2H-chromanes.
Keywords: Chromanochalcones, chromano dihydrochalcones, hydrogenation, NMR spectroscopy.
Introduction
Flavonoids are phenol derivatives present in substantial amounts (0.51.5%) in plants1
in which
they carry out important functions for their biochemistry and physiology.2
These compounds
contribute to color, flavor and processing characteristics important in many foods (vegetables,
fruits) and in drinks (tea, wine). Food from common plants contain from traces up to several
grams per kg fresh weight of flavanoids.3
Biological properties of flavonoids and their pharma-
ceutical potencies have been widely investigated and extensively reviewed during the past 30years.
4Dihydrochalcones comprise a small group of compounds chemically and biochemically
very closely related to chalcones. The utilization of certain dihydrochalcone derivatives and
related compounds as sweetening agents has been reported.5
Previously, we have isolated chalcones 5aa, 5ab, 5ba, and 5bb (Scheme 1) in our
laboratory from the Indian medicinal plant species crotalaria. Here we have undertaken the
synthesis of these dihydrochalcones. The aim of the current synthetic study was to provide clear
mailto:srmeneni@mail.uri.edumailto:srmeneni@mail.uri.edumailto:srmeneni@mail.uri.edu -
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and easy access to prenylated dihydrochalcones with the saturation and unsaturation in - and -
positions and also in the chromane part. Our strategy was the construction of 6-acetylchromanes
2a and 2b by condensation of 2,4-dihydroxyacetophenone (1) with isoprene in presence of
Amberlyst 15, followed by the condensation with methoxybenzaldehydes 3a,b to afford the
target chromanochalcones.6,7
Results and Discussion
2,4-Dihydroxyacetophenone (1) can be obtained from commercially available resorcinol by
reaction with acetyl chloride and zinc chloride. It was reacted with 2-methylbuta-1,3-diene in the
presence of sulfonic acid cation exchange resin Amberlyst 15 in THF to give two regioisomeric
acetylchromanes, 1-(5-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)ethanone (2a) and
1-(7-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)ethanone (2b) (Scheme 1).
R1 O
O
OCH3
R4
R3
R1 O
O
OCH3R3
R4
R1 O
O
OH
HO
Oamberlyst15,THF, heptane
1
R2
R2 R2
2a: R1 = OH, R2 = H; 2b: R1 = H, R2 = OH
3a: R3 = R4 = H; 3b: R3 = R4 = OCH3
4aa,ab,ba,bb 5aa,ab,ba,bb
2a,b
3a,b;
OCH3
R4
R3
OHC
Ba(OH)2, EtOH
R1 R2 R3 R4
OH
OH
H
H
H
H
OH
OH
H H
H H
OCH3 OCH3
OCH3 OCH3
aa
ab
ba
bb
4, 5
Pd/C,
HCO2NaMeOH
12
3
4 5
6
1'
2'3'
4'
5'
6'
4a
788a
Scheme 1.
Treatment of the 6-acetylchromanes 2a,b with methoxybenzaldehydes 3a (R3
= R4
= H)
and 3b (R3
= R4
= OMe) in basic media [Ba(OH)2 in EtOH] afforded the corresponding
chromanochalcones 4aa, 4ab and 4ba, 4bb, respectively. Except 4ab, all chalcones have beendescribed before.
8Finally, the respective dihydrochalcones 5 were synthesized by reduction of
chalcones 4 with sodium formate in Pd/C. Only 5ba has been reported in the literature.8
The structures of all compounds were determined by electron-impact mass spectrometry
and by 1D and 2D NMR spectroscopy (DEPT,1H,
1H-COSY, HMBC, HMQC). Thereby, all
1H
and13
C signals could be assigned, and the atomic connectivities were established unambiguously
(Tables 1 and 2). The easiest way to differentiate the regioisomers ofproducts 4 and 5 was the
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inspection of the two aromatic protons 7,8-H (aa, ab) and 5,8-H (ba, bb), respectively, which
are either in ortho- or in para-position with respect to each other; accordingly, these signals
appeared as doublets (J= 89 Hz) or as singlets (J< 1 Hz), respectively.
The1H NMR spectra of the chalcones show a signal for a chelated aromatic hydroxyl
group in between 13.0 and 14.0, and in addition signals of aromatic methoxyl groups and
aromatic protons. The two sharp doublets between 7.08.0 withJ= 15.3 Hz are characteristic
of the trans double bond of chalcones 4. All NMR data are compiled in Tables 1and 2.
Table 1.1H Chemical shifts and
1H,
1H coupling constantsJ[Hz] of compounds 2, 4, and 5; in
CDCl3 at 400.1 MHz. For atom numbering see structure 4 in Scheme 1.
Atom
Pos.2a 2b 4aa 4ab 5aa 5ab 4ba 4bb 5ba 5bb
2,2-
(CH3)2
1.34 s 1.35 s 1.36 s 1.37 s 1.34s 1.34 s 1.37 s 1.36 s 1.34 s 1.34 s
3 2.68 t 1.82 t 2.73 t 2.73 t 1.81t 1.80 t 1.84 t 1.83 t 1.81 t 1.80 t
4 1.81 t 2.75 t 1.83 t 1.82 t 2.68t 2.69 t 2.78 t 1.83 t 2.68 t 2.69 t
5 7.44 s 7.63 s 7.62 s 7.42 s 7.45 s
5-OH 13.11 s 13.96 s 14.08 s 13.18s 13.18 s
6-CH3CO 2.54 s 2.55 s
7 7.49 d
J7,8 =
8.9
7.69 d
J7,8 = 9
7.70 d
J7,8 = 9
7.49 d
J7,8 =
8
7.50 d
J7,8 = 9
7-OH 12.34 s 13.10 s 13.23 s 12.38 s 12.49 s
8 6.33 d 6.31 s 6.38 d 6.38 d 6.31 d 6.31 d 6.37 s 6.36 s 6.31 s 6.31 s
7.48 d
15.3
7.54 d
15.4
3.18 d 3.12 dd 7.47 d
15.4
7.49 d
15.4
3.18 dd 3.12
dd
7.86 d 8.17 d 2.98
dd
2.95 dd 7.83d 8.16 d 98 dd 2.95
dd
2 7.60 7.16 7.63 7.16
3 6.93 6.53 s 6.83 6.51 s 6.94 6.52 s 6.84 6.51 s
5 6.93 6.83 6.94 6.84
6 7.60 7.12 s 7.16 6.75 s 7.63 7.13 s 7.16 6.75 s
2-OCH3 3.91 s 3.82 s 3.91 s 3.82 s4-OCH3 3.86 s 3.96 s 3.78 s 3.88 s 3.81 s 3.95 s 3.79 s 3.88 s
5-OCH3 3.91 s 3.81 s 3.92 s 3.81 s
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Table 2.13
C Chemical shifts of compounds 2, 4, and 5; in CDCl3 at 100.6 MHz. For atom
numbering see structure 4 in Scheme 1.
Atom Pos. 2a 2b 4aa 4ab 5aa 5ab 4ba 4bb 5ba 5bb
2 75.8 75.8 75.7 75.7 75.7 76.1 75.9 75.8 75.8 76.1
2,2-(CH3)2 26.7 26.9 26.7 26.7 26.7 27.4 27.6 26.9 26.9 27.43 31.8 32.7 31.8 31.9 31.8 33.2 32.8 32.7 21.7 33.2
4 16.2 21.7 16.3 16.4 16.3 22.2 21.8 21.8 32.7 22.2
4a 109.0 112.7 109.3 109.3 109.1 109.1 112.6 112,4 112.6 114.9
5 162.6 132.2 164.0 164.0 162.8 162.8 131.0 131.0 131.4 132.2
6 112.6 113.9 112.8 113.0 112.1 112.1 114.2 114.3 113.5 113.3
7 129.5 162.8 128.4 128.4 128.7 128.7 164.1 164.0 163.0 162.0
8 109.1 104.6 109.0 108.9 109.1 109.1 104.9 104.8 104.7 105.0
8a 160.7 161.3 160.7 160.5 160.6 160.6 161.3 161.0 161.2 161.0
6-CH3CO 26.0 26.2
6-C=O 202.5 202.3 191.8 192.3 203.5 202.5 191.7 192.1 203.4 204.1
118.1 118.4 39.8 39.8 118.0 118.2 39.9 39.3
143.6 139.2 29.7 26.4 143.8 139.3 29.6 26.4
1 127.6 115.6 133.0 121.0 127.7 115.5 133.1 121.0
2 130.2 154.8 129.3 151.8 130.3 154.7 129.3 151.8
3 114.4 96.9 114.0 98.0 114.4 96.8 114.0 98.0
4 161.6 152.6 158.0 148.5 161.7 152.6 158.1 148.5
5 114.4 143.3 114.0 143.3 114.4 143.2 114.0 143.3
6 130.2 111.7 129.3 114.9 130.3 111.7 129.3 114.9
2-OCH3 56.6 56.9 56.7 56.94-OCH3 55.4 56.1 55.3 56.9 55.4 56.0 55.3 56.9
5-OCH3 56.3 56.9 56.3 56.9
Experimental Section
General Procedures. The NMR spectra of CDCl3 solutions were recorded using a Bruker DPX-
400 spectrometer (1H: 400.1 MHz;
13C: 100.6 MHz). Standard Bruker software was employed
for all one- and two-dimensional experiments.1H and
13C NMR spectroscopic data are compiled
in Tables 1 and 2. Electron impact mass spectra (70 eV) were obtained from a Finnigan MAT-
312 instrument. All solvents were purified and distilled prior to use. Column chromatography
was performed on silica gel (Merck 60, 70230 mesh). Thin-layer chromatography was
performed using pre-coated aluminum TLC plates of silica gel (60 F254).
1-(5-Hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)ethanone (2a) and 1-(7-hydroxy-
2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)ethanone (2b): To a stirred solution of Amber-
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chromen-6-yl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one (5bb): To a solution of chromano-
chalcone 4aa (250 mg, 0.74 mmol) and sodium formate (1.0 g, 14.7 mmol) in methanol (25 mL)
was added Pd/C(10%, 250 mg, 0.5 mmol), and the mixture was refluxed for 3045 min. After
the catalyst was removed by filtration, the solvent was distilled off, the residue was treated with
water, and the product was extracted with ether. The ether solution was washed with water, dried
over sodium sulfate, and the solvent was removed by evaporation. The residue 5aa (230 mg,
92%) was essentially pure to get spectral data; mp 102104 C. EI-MS: m/z (%) 341 [M++H]
(17), 323 (4), 205 (6), 178 (10), 149 (12), 134 (8), 121 (20), 49 (100). For1H and
13C NMR data
see Tables 1 and 2. Anal. Calcd for C21H24O4: C, 74.07; H, 7.09. Found: C, 74.11; H, 7.14.
5ab: The same treatment of compound 4ab afforded 5ab (210 mg, 83%);mp 126128 C. EI-
MS: m/z (%) 400 (54) [M+], 367 (100), 311 (14), 194 (45), 181 (51), 149 (28). For
1H and
13C
NMR data see Tables 1 and 2. Anal. Calcd for C23H28O6: C, 68.93; H, 7.04. Found: C, 68.98; H,
7.09.
5ba: Similarly, compound 4ba yielded 5ba (220 mg, 87%);mp 117118 C. EI-MS: m/z (%) =
340 [M+
] (17), 323 (4), 205 (6), 178 (10), 149 (12), 134 (8), 121 (20), 49 (100). For1
H and13
CNMR data see Tables 1 and 2. Anal. Calcd for C21H24O4: C, 74.07; H, 7.09. Found: C, 74.15; H,
7.17.
5bb: Compound 4bb gave 5bb (200mg, 79%);mp 138139 C. EI-MS: m/z (%) 400 (34) [M+],
205 (24), 181 (100), 151 (12). For1H and
13C NMR data see Tables 1 and 2. Anal. Calcd for
C23H28O6: C, 68.93; H, 7.04. Found: C, 68.10; H, 7.06.
Acknowledgements
M. S. Rao is grateful to the Institute of Organic Chemistry, University of Hannover, for support
during his research visit. This work has been performed within the project Biologically Active
Natural Products, Synthetic Diversity (Department of Chemistry, Hannover University).
References
1. Thompson, R. S.; Jacques, D.; Haslam, E.; Tanner, R. J. N.J. Chem. Soc., Perkin Trans. 1,1972, 1387.
2. (a) Harborne, J. B.; Mabry, T. J., Eds.; The Flavonoids,Advances in Research; Chapman &Hall: London, 1982. (b) Harborne, J. B., Ed.; The Flavonoids,Advances in Researchsince
1980; Chapman & Hall: London, 1988.
3. Singleton, V. L.: Advances in Food Research, Academic Press: New York, 1981; vol. 27,149.
4. Coll, M. D.; Coll, L.; Laencina, J.; Tomas-Barberan, F. A. Z. Lebensm.-Unters. Forsch. A.1998, 206, 404.
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5. Horowitz, R. M. Plant Flavonoids in Biology and Medicine, 1986, 163.6. Jain, A. C.; Lal, P., Seshadri, T. R. Tetrahedron1970, 26, 2631.7. Jain, A. C.; Lal, P., Seshadri, T. R.Ind. J. Chem. 1969, 7, 61.8. Ahluwalia, V. K.; Nayal, L., Kalia, N.; Bala, S.; Tehim, A. K. Ind. J. Chem. 1987, 26B, 384.
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